A comparative study of dietary curcumin, nanocurcumin, and other classical amyloid-binding dyes for labeling and imaging of amyloid plaques in brain tissue of 5×-familial Alzheimer’s disease mice

Abstract

Deposition of amyloid beta protein (Aβ) is a key component in the pathogenesis of Alzheimer's disease (AD). As an anti-amyloid natural polyphenol, curcumin (Cur) has been used as a therapy for AD. Its fluorescent activity, preferential binding to Aβ, as well as structural similarities with other traditional amyloid-binding dyes, make it a promising candidate for labeling and imaging of Aβ plaques in vivo. The present study was designed to test whether dietary Cur and nanocurcumin (NC) provide more sensitivity for labeling and imaging of Aβ plaques in brain tissues from the 5×-familial AD (5×FAD) mice than the classical Aβ-binding dyes, such as Congo red and Thioflavin-S. These comparisons were made in postmortem brain tissues from the 5×FAD mice. We observed that Cur and NC labeled Aβ plaques to the same degree as Aβ-specific antibody and to a greater extent than those of the classical amyloid-binding dyes. Cur and NC also labeled Aβ plaques in 5×FAD brain tissues when injected intraperitoneally. Nanomolar concentrations of Cur or NC are sufficient for labeling and imaging of Aβ plaques in 5×FAD brain tissue. Cur and NC also labeled different types of Aβ plaques, including core, neuritic, diffuse, and burned-out, to a greater degree than other amyloid-binding dyes. Therefore, Cur and or NC can be used as an alternative to Aβ-specific antibody for labeling and imaging of Aβ plaques ex vivo and in vivo. It can provide an easy and inexpensive means of detecting Aβ-plaque load in postmortem brain tissue of animal models of AD after anti-amyloid therapy.

Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer’s disease

“…Moreover, curcumin has high affinity to Aβ 42 , oligomers, and fibrils, which are tightly linked to AD (62)(63)(64)(65)(66)(67)(68). Curcumin intensely stains the central dense amyloid core in Aβ fibrils and plaques, as was also previously demonstrated in the brain of murine models of AD (101). Further, it labels the nonfibrillar forms of Aβ 40 and Aβ 42 based on its specific binding to the Aβ-hexapeptide 16 …”

Amyloid beta: structure, biology and structure-based therapeutic development

“…The first of these dyes was Congo red [335] , whose staining is linked to the presence of the cross-β structure of fibrils. Other amyloid dyes include iodine-sulfuric acid [336] , thioflavin T or S [337] , crystal violet [338] , methyl violet [339] , BTA-1 [340] , chrysamine G [341] , ANS (1-anilinonaphthalene-8-sulfonic acid) [342] , bisANS (4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid) [342] , Nile red [343] , K114 ((trans, trans)-1-bromo-2,5-bis (4-hydroxystyryl) benzene) [344] , FSB [345] , curcumin [346] , nanocurcumin [346] , and others. The thioflavin T staining method is widely used to identify and classify amyloid proteins in tissues.…”

Curcumin Modulates Molecular Chaperones and Autophagy-Lysosomal Pathways In Vitro after Exposure to Aβ42

“…The SLCP has greater cellular permeability and neuro protection as described previously [26,33,34]. Therefore, to compare the HSPs response, we treated the N2a cells with 1 μM of Cur and or SLCP for 24 h after exposed with Aβ42 (10 μM).…”

“…This SLCP consists of high-purity, long-chain phospholipid bilayer and a long-chain fatty acid solid lipid core, which coats the Cur. The SLCP have been well characterized by Maiti et al [34] and by Cole and Frautschy laboratory, at the University of California, Los Angeles in collaboration with Verdure Science [26,[35][36][37]. Details sources of all the antibodies used in this study are summarized in Table 1.…”

“…10 mM NaOH, DMSO, and PBS) due to their hydrophobic nature [34]. Therefore, the stock Cur, THC and SLCP were dissolved in methanol, and then diluted in the DMEM or MEM (methanol was <1%), before being added to the petri-dish containing the cells.…”